Clinical markers of immunotherapy outcomes in sarcoma

11578 Background: Despite immunotherapy’s promise in oncology, its use for sarcoma remains challenging. There are no sarcoma-specific biomarkers for immune checkpoint inhibitors (ICI). Previously, we reported our institutional experience highlighting ICI activity in 29 patients with sarcoma. In this updated study, we further explore responses to ICI based on ICI regimen and other covariates to identify significant clinical factors in sarcoma outcomes. Methods: Patients in the Ohio State University Sarcoma clinics were enrolled in the Sarcoma Retrospective ICI database from January 1, 2015 through November 1, 2021. Data included treatment regimen (single agent ICI or ICI+combination) along with covariates: stage, age, gender, histology, change in neutrophil-to-lymphocyte ratio (NLR), number of cycles of ICI and immune-related adverse events (irAE). ICI+combination was further categorized into ICI+chemotherapy, ICI+radiation, ICI+surgery or ICI+multiple (more than 2 modalities). Statistical analysis included log rank tests and proportional hazard regression. The primary objective was to evaluate overall survival (OS) and progression-free survival (PFS). Results: One hundred and thirty-five patients met inclusion criteria. We demonstrated improved OS in patients treated with ICI+combination (p = 0.014, median 64 weeks), but no effect on PFS (p = 0.471, median 31 weeks). Whether patients had received single agent or combination ICI, those who received more than 3 cycles of ICI had an improved OS and PFS (p < 0.05 for both). Patients who received single-agent ICI and whose change in NLR was less than 5 had an improved OS (p = 0.002); this was not seen in patients who received ICI+combination therapy (p = 0.441). Patients who had a documented irAE of dermatitis had improved OS but only in the ICI+combination cohort (p = 0.021). There were no differences in OS based on age, gender, histology or sub-categories of ICI+combination. This was not the case for PFS; patients who received any ICI regimen and were younger than 70 had a worse PFS (p = 0.036). Patients who developed an irAE, specifically colitis (p = 0.009), hepatitis (p = 0.048) and dermatitis (p = 0.003) had an improved PFS. There were no differences in PFS based on ICI regimen (or sub-categories of ICI+combination), gender, histology, change in NLR or grade of irAE. Our ICI cohort results are consistent with historical data from our previous study. Further, irAEs are similar to historical data. Conclusions: This retrospective study demonstrates that ICI+combination therapy can improve OS in sarcoma. This is consistent with our prior results of ICI in sarcoma. Benefits in OS/PFS were seen in patients who received more than 3 cycles of ICI and developed certain irAE. These results can direct the optimal duration of ICI therapy. Those with decreased change in NLR also had improved OS, demonstrating a potential prognostic biomarker. Further studies are needed to validate our findings.